The program of research in this proposal is in the general discipline of environmental pharmacology and examines in detail, using various tissue culture systems, animal models and man, the interacting effects of environmental chemicals, drugs, hormones, nutrition and genes of the biology and function of the heme-cytochrome P-450 systems. Tissue model systems are used extensively to study the biological impacts of environmental chemicals and newly developed techniques which include isolated nervous system cultures, alveolar macrophage cultures, erythroid differentiation (Friend-virus infected cells) and mitogen-stimulated lymphocytes show considerable promise in helping to elucidate the actions of organic pollutants and toxic metals, on cellular differentiation and metabolism. Study of the toxicity or organometals for heme-P-450 systems are planned and biological protective mechanisms against certain toxic metals are examined as is the role of nutritional factors in modifying (enhancing/increasing) the biological impacts of chemicals in man and animals.